Oral biofilm inhibitor

ABSTRACT

There is provided an oral biofilm inhibitor having an exceptional inhibitory effect on oral biofilm formation. It is an oral biofilm inhibitor comprising a curable composition containing an antimicrobial agent, wherein a compressive strength of a cured product formed by curing the composition is 150 MPa or less, and a content of the antimicrobial agent is 0.001 to 3% by weight. An oral biofilm inhibitor thus obtained is used for inhibiting biofilm formation in an oral cavity by applying a curable composition containing an antimicrobial agent to a dental defect site for allowing the composition to cure at the dental defect site, and then disintegrating the cured composition.

TECHNICAL FIELD

The present invention relates to an oral biofilm inhibitor.

BACKGROUND ART

It has been known that various bacteria and so forth present in an oralcavity cause oral diseases such as dental caries, periodontal disease,gingivitis and halitosis. Generally, in an oral cavity, many of oralbacteria exist not alone, but as a bacterial flora called as a biofilm.In the light of preventing oral diseases, it is, therefore, important toinhibit oral biofilm formation.

Patent Reference No. 1 has described a dental hydraulic temporary sealercomposition comprising 10 to 90% by weight of calcium sulfate, 5 to 40%by weight of a vinyl acetate resin, 1 to 40% by weight of an inorganicfiller, 1 to 30% by weight of an alcohol with a boiling point of 110° C.or higher and 0.001 to 5% by weight of a nonionic surfactant. Thereference has described that there can be provided a dental hydraulictemporary sealer composition which is significantly improved in initialcurability, sealability and filling operability in an oral cavitycompared to a conventional dental hydraulic temporary sealer. PatentReference No. 1 has, however, not described or implied inhibition ofbiofilm formation.

PRIOR ART REFERENCES Patent References

Patent Reference No. 1: JP 2011-213608 A

SUMMARY OF THE INVENTION Problems to be Solved by the Invention

To solve the above problems, an objective of the present invention is toprovide an oral biofilm inhibitor excellent for inhibiting oral biofilmformation.

Means for Solving the Problems

The above problems can be solved by providing an oral biofilm inhibitorcomprising a curable composition containing an antimicrobial agent,wherein a compressive strength of a cured product formed by curing thecomposition is 150 MPa or less, and a content of the antimicrobial agentis 0.001 to 3% by weight.

Here, preferred is the oral biofilm inhibitor used for inhibitingbiofilm formation in an oral cavity by applying a curable compositioncontaining an antimicrobial agent to a dental defect site for allowingthe composition to cure at the dental defect site, and thendisintegrating the cured composition.

The oral biofilm inhibitor as described above, wherein the curablecomposition is again applied to the site where the cured composition hasbeen disintegrated, is also a preferable embodiment of the presentinvention.

The above problems can be also solved by providing an oral biofilminhibitor kit comprising a curable composition and an antimicrobialagent, wherein a compressive strength of a cured product formed bycuring an oral biofilm inhibitor is 150 MPa or less, and the curablecomposition and the antimicrobial agent are blended for use such that acontent of the antimicrobial agent in the oral biofilm inhibitor comesto be 0.001 to 3% by weight.

The above problems can be also solved by providing an oral biofilminhibitor kit comprising a curable composition and a liquid agentcontaining water as a main component, wherein at least one of thecurable composition and the liquid agent containing water as a maincomponent comprises the antimicrobial agent; a compressive strength of acured product formed by curing the oral biofilm inhibitor is 150 MPa orless; and the curable composition and the liquid agent are blended foruse such that a content of the antimicrobial agent comes to be 0.001 to3% by weight.

The above problems can be also solved by providing a method forproducing an oral biofilm inhibitor comprising a curable compositioncontaining an antimicrobial agent, comprising blending the curablecomposition and the antimicrobial agent such that a content of theantimicrobial agent in the oral biofilm inhibitor comes to be 0.001 to3% by weight.

Effects of the Invention

According to the present invention, there can be provided an oralbiofilm inhibitor excellent for inhibiting oral biofilm formation.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a graph showing compressive strength of a cured product inExample 1, and Comparative Examples 1 and 2.

FIG. 2 is a photograph of histopathological examination in Example 1,and Comparative Examples 1 and 2.

FIG. 3 is a graph showing the amount of ATP in a culture medium after 6and 12 hours in Example 1, and Comparative Examples 1 and 2.

FIG. 4 is an electron microgram of the surface of a cured product afterimmersion in a culture medium in Example 1, and Comparative Examples 1and 2 (magnification: 1000 and 10000).

FIG. 5 is a graph showing compressive strength of a cured product inComparative Examples 3 to 5.

FIG. 6 is a graph showing the amount of ATP in a culture medium after 6and 12 hours in Comparative Examples 3 to 5.

FIG. 7 is an electron microgram of the surface of a cured product afterimmersion in a culture medium in Comparative Examples 3 to 5(magnification: 1000 and 10000).

FIG. 8 is a graph showing the amount of ATP in a culture medium after 6and 12 hours in Example 2, and Comparative Examples 6 and 7.

FIG. 9 is an electron microgram of the surface of a cured product afterimmersion in a culture medium in Example 2, and Comparative Examples 6and 7 (magnification: 1000 and 10000).

MODES FOR CARRYING OUT THE INVENTION

The present invention is characterized in an oral biofilm inhibitorcomprising a curable composition containing an antimicrobial agent,wherein a compressive strength of a cured product formed by curing thecomposition is 150 MPa or less, and a content of the antimicrobial agentis 0.001 to 3% by weight. In the present invention, it is extremelyimportant that a compressive strength of a cured product formed bycuring the composition is a particular value or less and a content ofthe antimicrobial agent in the inhibitor is within a particular range.We have found that an oral biofilm inhibitor of the present inventionexhibits excellent inhibitory effect to biofilm formation, only when theconditions described above are met.

It is important that a content of the antimicrobial agent in the oralbiofilm inhibitor of the present invention is 0.001 to 3% by weight. Ithas been observed that when a content of the antimicrobial agent iswithin this range, the inhibitor is antimicrobially effective in aculture medium and a biofilm is not formed on the surface of a curedproduct. If a content of the antimicrobial agent is more than 3% byweight, inhibiting biofilm formation is difficult. As shown in Exampleslater, when a cured product with a content of the antimicrobial agentbeing 5% by weight is immersed in a S. mutans culture medium,antimicrobial effect was observed in the culture medium but a biofilmwas formed on the surface of the cured product. Surprisingly, it hasbeen found for the first time by our investigation that when a contentof the antimicrobial agent in the inhibitor is increased, biofilminhibitory effect is rather lowered. It is, therefore, significant toemploy a formation that a content of the antimicrobial agent is 3% byweight or less.

It is generally known that many of cationic antimicrobial agents arebitter. In the light of suppressing bitterness when it is put into anoral cavity, a lower content of the antimicrobial agent is preferable.Seen from this point of view, a content of the antimicrobial agent ispreferably 2% by weight or less, more preferably 1% by weight or less.Furthermore, if a content of the antimicrobial agent is less than 0.001%by weight, biofilm formation cannot be inhibited, and a content of theantimicrobial agent is preferably 0.005% by weight or more, morepreferably 0.01% by weight or more.

Herein, there are no particular restrictions to the type of anantimicrobial agent. Examples of an antimicrobial agent include cationicantimicrobial agents such as cetylpyridinium chloride (CPC), thymol andisopropylmethylphenol (IPMP).

In an oral biofilm inhibitor of the present invention, it is alsoimportant that a compressive strength of a cured product formed bycuring a curable composition containing an antimicrobial agent is 150MPa or less. If a compressive strength is more than 150 MPa, biofilmformation cannot be inhibited, and a compressive strength is preferably100 MPa or less, more preferably 50 MPa or less, further preferably 25MPa or less, particularly preferably 10 MPa or less. If a compressivestrength is too low, formability may not be maintained. Therefore, it isgenerally 0.01 MPa or more, preferably 0.05 MPa or more. A compressivestrength of a cured product in the present invention is defined inaccordance with “compressive strength test” described in JIS T6602. Asseen from Examples later, three cured products are pressed at acrosshead speed of 2 mm/min and a load at the time of crush of the curedproducts is measured and an average is calculated to determine acompressive strength.

There are no particular restrictions to the type of a curablecomposition as long as a cured product formed by curing a curablecomposition containing an antimicrobial agent has a compressive strengthof 150 MPa or less. The curable composition is preferably at least oneof a hydraulic composition, a photocurable composition and athermosetting composition. Among these, a hydraulic composition is wellhandleable because it cures by reaction with a liquid agent containingwater as a main component. In this regard, a curable composition is morepreferably a hydraulic composition, further preferably, because it curesby reaction with water in saliva, a hydraulic composition containingcalcium sulfate as a main component. Herein, a liquid agent containingwater as a main component can be pure water or a liquid agent containingwater as a main component and other components. Furthermore, a maincomponent refers to a component with a content of generally 50% byweight or more, preferably 80% by weight or more.

There are no particular restrictions to the form of a curablecomposition before curing, and it is preferably a paste in the light ofeasy application to an oral cavity.

The oral biofilm inhibitor can contain a component other than anantimicrobial agent as long as the effects of the present invention arenot deteriorated; for example, a flavor, a colorant, a thickener can beappropriately added. A content of these components is generally 10% byweight or less, preferably 5% by weight or less.

Herein, preferred is an oral biofilm inhibitor used for inhibitingbiofilm formation in an oral cavity by applying a curable compositioncontaining an antimicrobial agent to a dental defect site for allowingthe composition to cure at the dental defect site, and thendisintegrating the cured composition.

An oral biofilm inhibitor of the present invention has moderatecompressive strength, so that the inhibitor may partly disintegrate, forexample, by mastication. Thus, owing to disintegration of the inhibitor,the antimicrobial agent contained in the inhibitor is released in anoral cavity. As a result, oral biofilm formation can be more effectivelyinhibited.

A preferable embodiment of the present invention is applying again acurable composition containing an antimicrobial agent to the site wherethe cured composition has been disintegrated. Thus, an oral cavity canbe consistently kept clean.

There are no particular restrictions to a method of applying a curablecomposition containing an antimicrobial agent to a dental defect site aslong as the dental defect site can be completely sealed. A dental defectsite can be a dental defect site due to dental caries or periodontaldisease, a dental defect site due to injury, a cavity or the like. Thereare also no restrictions to a method for curing a curable composition ata dental defect site. When the curable composition is a hydrauliccomposition containing calcium sulfate as a main component, it reactswith water in saliva and therefore, a curing method is convenient. Watercan be, if necessary, applied to the surface of the composition afterapplying the hydraulic composition to the dental defect site.

Another embodiment of the present invention is an oral biofilm inhibitorkit comprising a curable composition and an antimicrobial agent. Herein,a compressive strength of a cured product formed by curing the oralbiofilm inhibitor is 150 MPa or less. The kit is provided for use byblending the components such that a content of the antimicrobial agentin the oral biofilm inhibitor comes to be 0.001 to 3% by weight.

Another embodiment of the present invention is an oral biofilm inhibitorkit comprising a curable composition and a liquid agent containing wateras a main component. Here, at least one of the curable composition andthe liquid agent containing water as a main component contains anantimicrobial agent. A compressive strength of a cured product formed bycuring an oral biofilm inhibitor is 150 MPa or less. The kit is providedfor use by blending the components such that a content of anantimicrobial agent in the oral biofilm inhibitor comes to be 0.001 to3% by weight.

There are no particular restrictions to a method for producing an oralbiofilm inhibitor of the present invention; specifically, a curablecomposition and an antimicrobial agent are blended such that a contentof the antimicrobial agent in the oral biofilm inhibitor comes to be0.001 to 3% by weight. The curable composition and the antimicrobialagent can be blended by, but not limited to, manual mixing, a mixingdevice or the like. The curable composition and the antimicrobial agentcan be blended for preparing the inhibitor immediately beforeapplication to a dental defect site. Herein, when a liquid agentcontaining water as a main component is used, a liquid agent containingwater as a main component can be blended with a curable compositioncontaining an antimicrobial agent, or a liquid agent containing water asa main component and antimicrobial agent can be blended with a curablecomposition.

Since an oral biofilm inhibitor of the present invention is excellent ininhibitory effects on oral biofilm formation, it could be used tovarious applications. Supposed subjects are, in addition to patientswith an oral disease, immune-compromised patients (for example, patientswith cancer under therapy), elderly adults and the like. When a patientis immune-compromised, risk of developing various systemic diseases isincreased. Such a systemic disease that can be mentioned is, forexample, aspiration pneumonia. Aspiration pneumonia refers to a diseasewhere oral bacteria invade a lung through misswallowing and grow in thelung, causing inflammation. Invasion by oral bacteria into a lung doesnot necessarily lead to development of pneumonia, but when immunity iscompromised, risk of developing aspiration pneumonia is increased. Byapplying an oral biofilm inhibitor of the present invention to an oralcavity, various systemic diseases such as aspiration pneumonia can beprevented.

Since an oral biofilm inhibitor of the present invention can beconveniently used, it can be used not only in a dental clinic but alsoin home care. Furthermore, it can be used in a wide-scale disaster site.If a wide-scale disaster occurs, it becomes difficult to keep an oralcavity clean due to disrupted water supply, leading to deterioratedhygienic environment in the oral cavity. Thus, it may cause a systemicdisease as described above. Since an oral cavity can be consistentlykept clean by use an oral biofilm inhibitor of the present invention,the use of the inhibitor in a wide-scale disaster site offersparticularly numerous benefits.

EXAMPLES

The present invention will be further specifically described withreference to Examples.

Example 1

Production of a cured product

A cured product was produced as described below.

(1) 1.99 g of dental hydraulic temporary sealer (“Caviton”, from GCCorporation) and 0.01 g of cetylpyridinium chloride (hereinafter,sometimes abbreviated as “CPC”) were blended at room temperature to givea mixture.

(2) a mold with a diameter of 5 mm and a depth of 10 mm was filled withthe mixture obtained.

(3) this mold was immersed in distilled water.

(4) after immersion of the mold in distilled water for 24 hours, themold was removed from the distilled water.

(5) the removed mold was placed in a drying chamber (37° C.).

(6) after placing the mold in the drying chamber for 3 days, the moldwas removed from the drying chamber and the cylindrical cured productwas taken out from the mold.

Measurement of Strength

A compressive strength of the cured product obtained was measured inaccordance with “compressive strength test” described in JIS T6602. Themeasurement was conducted for three cured products; the cured productwas pressed at a crosshead speed of 2 mm/min and a load at the time ofcrush of the cured product was measured and an average was calculated.The cured product used for the measurement had an average diameter of5.1 mm and an average height of 10.6 mm. A measurement apparatus usedwas “Autograph AG-X 20 kN” from Shimadzu Corporation. As a result, acompressive strength per 5.1 mm diameter of the cured product was 1.31kgf/φ5.1 mm. It was converted to a compressive strength per unit area(MPa), which was 0.63 MPa. The results are shown in Table 1 and FIG. 1.

Evaluation of Irritation to Oral Mucous Membrane

For evaluating irritation to oral mucous membrane of a cured productextract, a buccal-pouch mucous membrane irritation examination using aSyrian hamster was conducted. A cured product extract was obtained byextracting the cured product with 200 mL of PBS per 1 g of the productat 37° C. for 12 hours. The cured product extract was applied 4 timesevery 1 hour to the inside of the right buccal pouch of each of fiveSyrian hamsters. The buccal pouch mucous membrane was visually observedfor up to 24 hours after the final application and at the end of visualobservation, the animal was euthanized by overdose of pentobarbital.Then, both right and left buccal pouches were isolated and subjected tohistopathological examination. The left buccal pouch was used as anuntreated control.

Examination name: buccal pouch mucous membrane irritation examination ofa CPC-containing Caviton extract using hamsters

Examination number: G102 (590-005), GLP: not applicable

Examiner: Public Interest Incorporated Foundation, BioSafety ResearchCenter

As a result, the cured product extract was judged to be nonirritating tothe buccal pouch mucous membrane of the syrian hamster. FIG. 2(Cav-CPC0.5) is a photograph of the histopathological examination.

Evaluation of Antimicrobial Effect

Preparation of an S. mutans Culture Medium

An S. mutans culture medium was prepared as described below.

(1) Streptococcus mutans ATCC25175 strain was cultured under aerobicconditions at 37° C., using Bacto™ Brain Heart Infusion (Becton,Dickinson and Company, Sparks, Md., USA) liquid culture medium.

(2) After cultivation to a logarithmic growth phase under aerobicconditions, an absorbance at a wavelength of 660 nm (A660) was measuredusing an absorption spectrometer (“SPECTRONIC 20A”, from ShimadzuCorporation), and the cultivated medium was diluted to 1×10⁵ cfu/mL withthe above liquid medium, to prepare a bacterial suspension.

Evaluation of Bacterial Proliferation Activity

12 milliliter of the culture medium prepared was taken and kept at 37°C., and the cured product was immersed in the culture medium. 48 hoursafter immersion of the cured product in the culture medium, the curedproduct was taken off from the culture medium. Here, for measuring theamount of ATP in the culture medium, the culture medium was taken 6 and12 hours after immersion of the cured product in the culture medium.Then, the amount of ATP in the culture medium was measured using atesting kit and a tester (“Lucifer HS set” and “Lumitester C-110” fromKikkoman Biochemifa Company). The amount of ATP in the culture medium at6 and 12 hours is shown in Table 1 and FIG. 3. Table 1 and FIG. 3 showthat the smaller RLU (luminescence amount) is, the more bacterialproliferation is suppressed. In FIG. 3, “Cont” indicates RLU of theculture medium after 6 hours (average: 37206.0, standard deviation:1857.2) and after 12 hours (average: 689864.7, standard deviation:38395.5) when the cured product was not immersed in the culture medium.

Evaluation of Biofilm Inhibition

Microscopic Observation

The surface of the cured product removed from the culture medium wasobserved by a field emission-type scanning electron microscope. FIG. 4shows an electron microgram at a magnification of 1000 and an electronmicrogram at a magnification of 10000. For the electron micrograms(“Cav-CPC0.5”, “×10000”), the presence of bacteria on the surface of thecured product was visually observed. As a result, no bacteria wereobserved and biofilm was not formed on the cured product. The fieldemission-type scanning electron microscope used was “FE-SEM DS-720” fromTopcon Corporation.

Example 2

“Evaluation of bacterial proliferation activity” and “Evaluation ofbiofilm inhibition” were conducted as described in Example 1, using aCandida albicans culture medium prepared as described below. The amountof ATP in the culture medium at 6 and 12 hours is shown in Table 2 andFIG. 8. FIG. 9 shows an electron microgram at a magnification of 1000and an electron microgram at a magnification of 10000 (Cav-CPC0.5). As aresult, no bacteria were observed and biofilm was not formed on thecured product.

(1) C. albicans (clinical isolate) was cultured under aerobic conditionsat 37° C., using Bacto™ Brain Heart Infusion (Becton, Dickinson andCompany, Sparks, Md., USA) liquid culture medium.

(2) After cultivation to a logarithmic growth phase under aerobicconditions, an absorbance at a wavelength of 660 nm (A660) was measuredusing an absorption spectrometer (“miniphoto 518R”, from TAITECCorporation), and the cultivated medium was diluted to 1×10⁵ cfu/mL withthe above liquid medium, to prepare a bacterial suspension.

Comparative Example 1

A cured product was produced as described in Example 1, except that 1.90g of Caviton and 0.1 g of CPC were blended at room temperature to afforda mixture in “Production of a cured product” in Example 1. Then,“Measurement of strength”, “Evaluation of antimicrobial effect” and“Evaluation of biofilm inhibition” were conducted as described inExample 1. The results obtained are shown in Table 1 and FIGS. 1, 3 and4. As shown in FIG. 4, the presence of bacteria on the surface of thecured product was visually observed for the electron microgram obtained(“Cav-CPC5”, “×10000”). As a result, in the area of the electronmicrogram (13 μm×9 μm), 45 bacteria (arrow in the photograph) wereobserved, indicating biofilm formation on the cured product.Furthermore, “Evaluation of irritation to oral mucous membrane” wasconducted as described in Example 1. As a result, the cured productextract was judged to be nonirritating to the buccal pouch mucousmembrane of the syrian hamster. FIG. 2 (Cav-CPC5) is a photograph of thehistopathological examination.

Comparative Example 2

A cured product was produced as described in Example 1, except that CPCwas absent and 2 g of Caviton was used in “Production of a curedproduct” in Example 1. Furthermore, “Measurement of strength”,“Evaluation of antimicrobial effect” and “Evaluation of biofilminhibition” were conducted as described in Example 1. The resultsobtained are shown in Table 1 and FIGS. 1, 3 and 4. As shown in FIG. 4,the presence of bacteria on the surface of the cured product wasvisually observed for the electron microgram obtained (“Cav-CPC0”,“×10000”). As a result, in the area of the electron microgram (13 μm×9μm), 208 bacteria (arrow in the photograph) were observed, indicatingbiofilm formation on the cured product. Furthermore, “Evaluation ofirritation to oral mucous membrane” was conducted as described inExample 1. As a result, the cured product extract was judged to benonirritating to the buccal pouch mucous membrane of the Syrian hamster.FIG. 2 (Cav-CPC0) is a photograph of the histopathological examination.

Comparative Example 3

A cured product was produced as described in Example 1, except that in“Production of a cured product” in Example 1, a dental hydraulictemporary sealer was changed to “Panavia F” from Morita Corporation and0.4975 g of Panavia F and 0.0025 g of CPC were blended at roomtemperature to afford a mixture. Then, “Measurement of strength”,“Evaluation of antimicrobial effect” and “Evaluation of biofilminhibition” were conducted as described in Example 1. The resultsobtained are shown in Table 1 and FIGS. 5 to 7. In Comparative Examples3 to 5, an S. mutans culture medium was newly prepared as described inExample 1. In FIG. 6, “Cont” indicates RLU of the culture medium after 6hours (average: 33152, standard deviation: 433) and after 12 hours(average: 682856, standard deviation: 44861) when the cured product wasnot immersed in the culture medium. As shown in FIG. 7, the presence ofbacteria on the surface of the cured product was visually observed forthe electron microgram obtained (“Pana-CPC0.5”, “×10000”). As a result,in the area of the electron microgram (13 μm×9 μm), more than 300bacteria were observed, indicating biofilm formation on the curedproduct.

Comparative Example 4

A cured product was produced as described in Example 1, except that in“Production of a cured product” in Example 1, a dental hydraulictemporary sealer was changed to “Panavia F” from Morita Corporation and0.475 g of Panavia F and 0.025 g of CPC were blended at room temperatureto afford a mixture. Then, “Measurement of strength”, “Evaluation ofantimicrobial effect” and “Evaluation of biofilm inhibition” wereconducted as described in Example 1. The results obtained are shown inTable 1 and FIGS. 5 to 7. As shown in FIG. 7, the presence of bacteriaon the surface of the cured product was visually observed for theelectron microgram obtained (“Pana-CPC5”, “×10000”). As a result, in thearea of the electron microgram (13 μm×9 μm), 60 bacteria were observed,indicating biofilm formation on the cured product.

Comparative Example 5

A cured product was produced as described in Example 1 , except that in“Production of a cured product” in Example 1 , a dental hydraulictemporary sealer was changed to “Panavia F” from Morita Corporation andCPC was absent and 0.5 g of Panavia F was used. Then, “Measurement ofstrength”, “Evaluation of antimicrobial effect” and “Evaluation ofbiofilm inhibition” were conducted as described in Example 1 . Theresults obtained are shown in Table 1 and FIGS. 5 to 7. As shown in FIG.7, the presence of bacteria on the surface of the cured product wasvisually observed for the electron microgram obtained (“Pana-CPC0”,“×10000”). As a result, in the area of the electron microgram (13 μm×9μm), more than 300 bacteria were observed, indicating biofilm formationon the cured product.

Comparative Example 6

A cured product was produced as described in Example 1, except that in“Production of a cured product” in Example 1, 1.90 g of Caviton and 0.1g of CPC were blended at room temperature to afford a mixture. Then,“Evaluation of bacterial proliferation activity” and “Evaluation ofbiofilm inhibition” were conducted as described in Example 1, using theCandida albicans culture medium prepared in Example 2. The amount of ATPin the culture medium at 6 and 12 hours is shown in Table 2 and FIG. 8.FIG. 9 shows an electron microgram at a magnification of 1000 and anelectron microgram at a magnification of 10000 (Cav-CPC5). As a result,in the area of the electron microgram (13 μm×9 μm), more than 300bacteria (the arrow in the photograph) were observed, indicating biofilmformation on the cured product.

Comparative Example 7

A cured product was produced as described in Example 1, except that in“Production of a cured product” in Example 1, CPC was absent and 2 g ofCaviton was used. Then, “Evaluation of bacterial proliferation activity”and “Evaluation of biofilm inhibition” were conducted as described inExample 1, using the Candida albicans culture medium prepared in Example2. The amount of ATP in the culture medium at 6 and 12 hours is shown inTable 2 and FIG. 8. FIG. 9 shows an electron microgram at amagnification of 1000 and an electron microgram at a magnification of10000 (Cav-CPC0). As a result, in the area of the electron microgram (13μm×9 μm), more than 300 bacteria (the arrow in the photograph) wereobserved, indicating biofilm formation on the cured product.

TABLE 1 Compression strength Cured product (kgf/ϕ5 mm, MPa) Antimicro-RLU Standard Curable bial agent after 6 hours after 12 hours Averagedeviation composition (% by Standard Standard kgf/φ5 kgf/φ5 No. of(brand) weight) Notation Average deviation Average deviation mm MPa mmMPa bacteria Example 1 Caviton 0.5 Cav-CPC0.5 251.0 84.9 33.7 11.6 1.310.63 0.11 0.05 0 Comparative Caviton 5 Cav-CPC5 183.7 108.2 32.7 8.44.06 1.95 0.30 0.14 45 Example 1 Comparative Caviton 0 Cav-CPC0 31772.710064.1 501523.0 142926.7 1.43 0.69 0.22 0.10 208 Example 2 ComparativePanavia F 0.5 Pana-CPC0.5 24763 11415 438532 263885 456.29 223.30 7.786.40 more Example 3 than 300 Comparative Panavia F 5 Pana-CPC5 25 27 155 326.57 160.86 1.35 2.41 60 Example 4 Comparative Panavia F 0 Pana-CPC033485 3925 716111 35169 468.76 227.11 25.96 23.92 More Example 5 than300

TABLE 2 Cured product Antimicrobial RLU Curable agent after 6 hoursafter 12 hours composition (% by Standard Standard No. of (brand)weight) Notation Average deviation Average deviation bacteria Example 2Caviton 0.5 Cav-CPC0.5 17 6 30 14 0 Comparative Caviton 5 Cav-CPC5 10 370 18 more Example 6 than 300 Comparative Caviton 0 Cav-CPC0 74514256511 5489307 235605 more Example 7 than 300

The invention claimed is:
 1. An oral biofilm inhibitor consisting of acurable composition containing cetylpyridinium chloride in paste formand which is at least one of a hydraulic composition, a photocurablecomposition or a thermosetting composition, wherein a compressivestrength of a cured product formed by curing the composition is 10 MPaor less, and a content of the cetylpyridinium chloride is 0.001 to 3% byweight.
 2. The oral biofilm inhibitor according to claim 1, used forinhibiting biofilm formation in an oral cavity by applying the curablecomposition containing the cetylpyridinium chloride to a dental defectsite for allowing the composition to cure at the dental defect site, andthen disintegrating the cured composition.
 3. The oral biofilm inhibitoraccording to claim 2, wherein the curable composition is again appliedto the site where the cured composition has been disintegrated.
 4. Anoral biofilm inhibitor kit comprising a curable composition andcetylpyridinium chloride in paste form and which is at least one of ahydraulic composition, a photocurable composition or a thermosettingcomposition, wherein a compressive strength of a cured product formed bycuring an oral biofilm inhibitor is 10 MPa or less, and the curablecomposition and the cetylpyridinium chloride are blended for use suchthat a content of the cetylpyridinium chloride in the oral biofilminhibitor comes to be 0.001 to 3% by weight.
 5. An oral biofilminhibitor kit comprising a curable composition in paste form which is atleast one of a hydraulic composition, a photocurable composition or athermosetting composition and a liquid agent containing water as a maincomponent, wherein at least one of the curable composition and theliquid agent containing water as a main component comprises thecetylpyridinium chloride, a compressive strength of a cured productformed by curing the oral biofilm inhibitor is 10 MPa or less, and thecurable composition and the liquid agent are blended for use such that acontent of the cetylpyridinium chloride comes to be 0.001 to 3% byweight.
 6. A method for producing an oral biofilm inhibitor comprising acurable composition containing cetylpyridinium chloride according toclaim 1, comprising blending the curable composition and thecetylpyridinium chloride such that a content of the cetylpyridiniumchloride in the oral biofilm inhibitor comes to be 0.001 to 3% byweight.
 7. A method for producing an oral biofilm inhibitor comprising acurable composition containing cetylpyridinium chloride according toclaim 2, comprising blending the curable composition and thecetylpyridinium chloride such that a content of the cetylpyridiniumchloride in the oral biofilm inhibitor comes to be 0.001 to 3% byweight.
 8. A method for producing an oral biofilm inhibitor comprising acurable composition containing cetylpyridinium chloride according toclaim 3, comprising blending the curable composition and thecetylpyridinium chloride such that a content of the cetylpyridiniumchloride in the oral biofilm inhibitor comes to be 0.001 to 3% byweight.